Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions

Beach, Robert E.; Watts, Bruns A.; Good, David W.; Benedict, Claude R.; DuBose, Thomas D.

doi:10.1038/ki.1991.105

Cited by 37 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that diffusional loss of oxygen from the descending vasa recta to AVR could be responsible for the low oxygen tension found in the renal medulla (3,4). The MTAL is especially vulnerable to hypoxic damage (22,23) and has been shown to generate adenosine in response (9). The close proximity of the site of adenosine production to OMDVR on the vascular bundle periphery might provide a mechanism for the MTAL to enhance its own perfusion and oxygenation through dilation of these vessels.…”

Section: Discussionmentioning

confidence: 99%

“…However, within the renal medulla, evidence favors a role for adenosine to act as a vasodilator (7,8). Beach et al have shown that the MTAL releases adenosine under hypoxic conditions (9). It has also been shown that interstitially administered adenosine improves medullary oxygenation (10) subsequent to increases in medullary blood flow (8).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat.

Silldorff¹,

Kreisberg²,

Pallone³

1996

J. Clin. Invest.

View full text Add to dashboard Cite

Adenosine is generated within the renal medulla under hypoxic conditions and is known to induce net vasoconstriction within the renal cortex while increasing medullary blood flow and oxygenation. To test the hypothesis that vasoconstriction of outer medullary descending vasa recta (OMDVR) is modulated by adenosine, we examined the effects of adenosine and adenosine A 1 and A 2 receptor subtype agonists on in vitro perfused control and preconstricted rat OMDVR. Constriction with angiotensin II (ANG II, 10 Ϫ 9 M) was attenuated by adenosine in a concentration-dependent manner (EC 50 to 10 Ϫ 5 M) elicited a biphasic response. Additionally, cyclohexyladenosine (10 Ϫ 6 M) caused vasoconstriction and CGS-21680 (10 Ϫ 6 M) had no effect on untreated vessels. Finally, an influence of ANG II receptor stimulation on adenosine A 1 receptor-mediated vasoconstriction could not be shown. These data suggest that OMDVR possess both A 1 and A 2 adenosine receptors and that they mediate constriction and dilatation, respectively. We conclude that adenosine is a potent modulator of OMDVR vasomotor tone and that its net effect is dependent upon local concentrations. ( J. Clin. Invest. 1996. 98:18-23.)

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat.

Silldorff¹,

Kreisberg²,

Pallone³

1996

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…related to electrolyte transport (21). Thus the kidney makes no exception with respect to enhanced adenosine generation and cellular release following ATP breakdown during oxygen deficiency or enhanced organ work.…”

Section: Normoxia and Ischemiamentioning

confidence: 99%

Adenosine and Kidney Function

Vallon

Mühlbauer²,

Oßwald³

2006

Physiological Reviews

396

379

View full text Add to dashboard Cite

In this review we outline the unique effects of the autacoid adenosine in the kidney. Adenosine is present in the cytosol of renal cells and in the extracellular space of normoxic kidneys. Extracellular adenosine can derive from cellular adenosine release or extracellular breakdown of ATP, AMP, or cAMP. It is generated at enhanced rates when tubular NaCl reabsorption and thus transport work increase or when hypoxia is induced. Extracellular adenosine acts on adenosine receptor subtypes in the cell membranes to affect vascular and tubular functions. Adenosine lowers glomerular filtration rate (GFR) by constricting afferent arterioles, especially in superficial nephrons, and acts as a mediator of the tubuloglomerular feedback, i.e., a mechanism that coordinates GFR and tubular transport. In contrast, it leads to vasodilation in deep cortex and medulla. Moreover, adenosine tonically inhibits the renal release of renin and stimulates NaCl transport in the cortical proximal tubule but inhibits it in medullary segments including the medullary thick ascending limb. These differential effects of adenosine are subsequently analyzed in a more integrative way in the context of intrarenal metabolic regulation of kidney function, and potential pathophysiological consequences are outlined.

show abstract

“…Pretreatment of medullary tissue strips with the P2 receptor antagonist suramin (albeit it is a relatively nonspecific antagonist) substantially blunted the cross talk from mTAL (141), indicating a role for P2Y or P2X receptors in the regulation of MBF (11). ATP and related nucleotides and PGE are known to be released in the renal outer medulla (8,14,23,60,102,148,172,173). Although it has been found that exogenous ATP stimulates pericytes and constricts VR (36), the complex role played by ATP and adenosine in the in vivo regulation of MBF and in tubulovascular cross talk remains to be explored.…”

Section: Excess O 2 ·ϫ and H 2 O 2 Production Relative To No In Mtal mentioning

confidence: 99%

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Cowley

Abe

Mori

et al. 2015

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

logical evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na ϩ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension.superoxide (O 2 ·Ϫ ); hydrogen peroxide (H2O2); nitric oxide (NO); NAD(P)H oxidase; mTAL; medullary blood flow; kidney; Dahl SS rats REACTIVE OXYGEN SPECIES (ROS) are chemically reactive molecules derived from oxygen, whose role as mediators of intracellular signaling cascades is well recognized. The following is a brief review of physiological data linking superoxide (O 2 ·Ϫ ), hydrogen peroxide (H 2 O 2 ), and nitric oxide (NO) production in the medullary thick ascending limbs of Henle (mTAL) to sodium (Na ϩ ) homeostasis, the regulation of medullary blood flow (MBF), and the long-term regulation of arterial blood pressure. MBF to the renal medulla can be importantly controlled by the constriction and dilation of the descending vasa recta (VR) capillaries, which branch from the efferent arterioles of the juxtamedullary glomeruli (49, 147, 149) and whose tone is controlled by the smooth muscle-like pericytes (49, 90, 146 -149). The role of NO cross talk from mTAL to surrounding VR in the renal medulla has been reviewed in detail elsewhere (19, 33) and will be discussed here largely with regard to its ROS-related counterregulatory functions. The present review will first summarize data showing that either the excess endogenous production or reduced scavenging of O 2 ·Ϫ or H 2 O 2 within the renal medulla results in a decrease in MBF and Na ϩ excretion, leading to hypertension and renal injury. Second, evidence will be summarized supporting the hypothesis that a high dietary salt intake results in increased luminal flow and delivery of NaCl to the mTAL, thereby signaling via both mechanical forces (stretch and shear) and increased Na ϩ transport, an increased mitochondrial and membrane NA-D(P)H oxidase production of O 2 ·Ϫ and H 2 O 2 . Third, studies will be reviewed showing that reduction of MBF leads to hypertension a...

show abstract

Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions

Cited by 37 publications

References 30 publications

Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat.

Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat.

Adenosine and Kidney Function

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Contact Info

Product

Resources

About